MDH2 (malate dehydrogenase 2)

Gene

• Entrez ID: 4191
• Gene name: Malate dehydrogenase 2
• Gene symbol: MDH2
• Synonyms (NCBI Gene): DEE51, EIEE51, M-MDH, MDH, MGC:3559, MOR1
• Chromosome: 7
• Chromosome location: 7q11.23
• Summary: Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the mitochondria and may play pivotal roles in the malate-

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs373968974	G>A	Conflicting-interpretations-of-pathogenicity	Missense variant, genic downstream transcript variant, coding sequence variant
rs375002796	C>G,T	Pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant
rs782308462	G>A	Pathogenic	Coding sequence variant, intron variant, missense variant, genic downstream transcript variant
rs1057519566	C>T	Pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant
rs1057519567	G>-	Pathogenic	Genic downstream transcript variant, coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT046682	hsa-miR-222-3p	CLASH	23622248
MIRT046217	hsa-miR-27b-3p	CLASH	23622248
MIRT044824	hsa-miR-320a	CLASH	23622248
MIRT042426	hsa-miR-425-3p	CLASH	23622248
MIRT041647	hsa-miR-484	CLASH	23622248
MIRT041283	hsa-miR-193b-3p	CLASH	23622248
MIRT039952	hsa-miR-615-3p	CLASH	23622248
MIRT035981	hsa-miR-1301-3p	CLASH	23622248
MIRT041283	hsa-miR-193b-3p	PAR-CLIP	27292025
MIRT1138619	hsa-miR-205	CLIP-seq
MIRT1138620	hsa-miR-2276	CLIP-seq
MIRT1138621	hsa-miR-3119	CLIP-seq
MIRT1138622	hsa-miR-3163	CLIP-seq
MIRT1138623	hsa-miR-4668-3p	CLIP-seq
MIRT1138624	hsa-miR-4686	CLIP-seq
MIRT1138625	hsa-miR-4772-3p	CLIP-seq
MIRT1138626	hsa-miR-4787-3p	CLIP-seq
MIRT1138627	hsa-miR-891a	CLIP-seq
MIRT2039330	hsa-miR-101	CLIP-seq
MIRT2039331	hsa-miR-1272	CLIP-seq
MIRT2039332	hsa-miR-144	CLIP-seq
MIRT1138619	hsa-miR-205	CLIP-seq
MIRT2039333	hsa-miR-2964a-5p	CLIP-seq
MIRT2039334	hsa-miR-3202	CLIP-seq
MIRT2039335	hsa-miR-3682-3p	CLIP-seq
MIRT2039336	hsa-miR-3910	CLIP-seq
MIRT2039337	hsa-miR-4533	CLIP-seq
MIRT1138626	hsa-miR-4787-3p	CLIP-seq
MIRT2039330	hsa-miR-101	CLIP-seq
MIRT2039331	hsa-miR-1272	CLIP-seq
MIRT2039332	hsa-miR-144	CLIP-seq
MIRT1138619	hsa-miR-205	CLIP-seq
MIRT1138620	hsa-miR-2276	CLIP-seq
MIRT2039333	hsa-miR-2964a-5p	CLIP-seq
MIRT2039334	hsa-miR-3202	CLIP-seq
MIRT2039335	hsa-miR-3682-3p	CLIP-seq
MIRT2039336	hsa-miR-3910	CLIP-seq
MIRT2039337	hsa-miR-4533	CLIP-seq
MIRT1138624	hsa-miR-4686	CLIP-seq
MIRT1138625	hsa-miR-4772-3p	CLIP-seq
MIRT1138626	hsa-miR-4787-3p	CLIP-seq
MIRT2269413	hsa-miR-520d-5p	CLIP-seq
MIRT2269414	hsa-miR-524-5p	CLIP-seq
MIRT2269415	hsa-miR-561	CLIP-seq
MIRT1138627	hsa-miR-891a	CLIP-seq
MIRT1138626	hsa-miR-4787-3p	CLIP-seq
MIRT2568593	hsa-miR-193b	CLIP-seq
MIRT1138619	hsa-miR-205	CLIP-seq
MIRT2568594	hsa-miR-4701-5p	CLIP-seq
MIRT2568595	hsa-miR-588	CLIP-seq
MIRT2568593	hsa-miR-193b	CLIP-seq
MIRT1138619	hsa-miR-205	CLIP-seq
MIRT2568594	hsa-miR-4701-5p	CLIP-seq
MIRT2568595	hsa-miR-588	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003723	Function	RNA binding	HDA	22658674, 22681889
GO:0003824	Function	Catalytic activity	IEA
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005737	Component	Cytoplasm	IBA
GO:0005739	Component	Mitochondrion	HDA	20833797
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	16740313
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006094	Process	Gluconeogenesis	IEA
GO:0006099	Process	Tricarboxylic acid cycle	IBA
GO:0006099	Process	Tricarboxylic acid cycle	IEA
GO:0006099	Process	Tricarboxylic acid cycle	IMP	37647199
GO:0006099	Process	Tricarboxylic acid cycle	TAS
GO:0006108	Process	Malate metabolic process	IDA	16740313
GO:0006108	Process	Malate metabolic process	IEA
GO:0006108	Process	Malate metabolic process	IMP	6576816
GO:0009060	Process	Aerobic respiration	IDA	27989324
GO:0016020	Component	Membrane	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016615	Function	Malate dehydrogenase activity	IEA
GO:0016616	Function	Oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	IEA
GO:0019674	Process	NAD+ metabolic process	IEA
GO:0019752	Process	Carboxylic acid metabolic process	IEA
GO:0030060	Function	L-malate dehydrogenase (NAD+) activity	EXP	16740313
GO:0030060	Function	L-malate dehydrogenase (NAD+) activity	IBA
GO:0030060	Function	L-malate dehydrogenase (NAD+) activity	IDA	16740313, 27989324
GO:0030060	Function	L-malate dehydrogenase (NAD+) activity	IEA
GO:0030060	Function	L-malate dehydrogenase (NAD+) activity	IMP	6576816
GO:0042802	Function	Identical protein binding	IEA
GO:0043490	Process	Malate-aspartate shuttle	IEA
GO:0043490	Process	Malate-aspartate shuttle	IMP	37647199
GO:0043490	Process	Malate-aspartate shuttle	TAS
GO:0046554	Function	L-malate dehydrogenase (NADP+) activity	IEA
GO:0070062	Component	Extracellular exosome	HDA	19056867, 20458337, 23533145

Other IDs

• MIM: 154100
• HGNC: 6971
• e!Ensembl: ENSG00000146701

Protein

• UniProt ID: P40926
• Protein name: Malate dehydrogenase, mitochondrial (EC 1.1.1.37)
• PDB: 2DFD, 4WLE, 4WLF, 4WLN, 4WLO, 4WLU, 4WLV
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00056	Ldh_1_N	25 → 168	lactate/malate dehydrogenase, NAD binding domain	Family
  PF02866	Ldh_1_C	170 → 334	lactate/malate dehydrogenase, alpha/beta C-terminal domain	Domain

• Sequence:

  MLSALARPASAALRRSFSTSAQNNAKVAVLGASGGIGQPLSLLLKNSPLVSRLTLYDIAH
  TPGVAADLSHIETKAAVKGYLGPEQLPDCLKGCDVVVIPAGVPRKPGMTRDDLFNTNATI
  VATLTAACAQHCPEAMICVIANPVNSTIPITAEVFKKHGVYNPNKIFGVTTLDIVRANTF
  VAELKGLDPARVNVPVIGGHAGKTIIPLISQCTPKVDFPQDQLTALTGRIQEAGTEVVKA
  KAGAGSATLSMAYAGARFVFSLVDAMNGKEGVVECSFVKSQETECTYFSTPLLLGKKGIE
  KNLGIGKVSSFEEKMISDAIPELKASIKKGEDFVKTLK

• Sequence length: 338

Pathways

KEGG:

Citrate cycle (TCA cycle)
Cysteine and methionine metabolism
Pyruvate metabolism
Glyoxylate and dicarboxylate metabolism
Metabolic pathways
Carbon metabolism

Reactome:

Gluconeogenesis
Citric acid cycle (TCA cycle)

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Developmental and epileptic encephalopathy, 51	Likely pathogenic; Pathogenic	rs782759642, rs782048786, rs1057519566, rs1057519567, rs782308462	RCV005032132 RCV002468746 RCV000417059 RCV000417042 RCV000417051
Infantile encephalopathy	Pathogenic	rs1057519566, rs1057519567	RCV000496994 RCV000509017

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Benign	rs11538801	RCV005929808
Adrenocortical carcinoma, hereditary	Benign	rs11538801	RCV005929812
Cervical cancer	Benign	rs11538801, rs142812282	RCV005929813 RCV005904363
Cholangiocarcinoma	Benign	rs11538801	RCV005929827
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign	rs11538801	RCV005929830
Clear cell carcinoma of kidney	Benign	rs11538801, rs142812282	RCV005929815 RCV005904364
Colon adenocarcinoma	Benign	rs11538801, rs142812282	RCV005929807 RCV005904360
Developmental and epileptic encephalopathy, 1	Conflicting classifications of pathogenicity	rs782408477	RCV004809920
Familial pancreatic carcinoma	Benign	rs11538801	RCV005929817
Gastric cancer	Benign	rs11538801	RCV005929820
Hepatocellular carcinoma	Benign; Likely benign	rs11538801, rs201575534	RCV005929809 RCV005907399
Hereditary pheochromocytoma and paraganglioma	Uncertain significance	rs141539461	RCV005601825
Lung cancer	Benign	rs11538801, rs142812282	RCV005929828 RCV005904368
Lymphoma	Benign	rs11538801	RCV005929821
Malignant lymphoma, large B-cell, diffuse	Benign	rs11538801, rs142812282	RCV005929818 RCV005904365
Malignant tumor of esophagus	Benign	rs11538801, rs142812282	RCV005929810 RCV005904361
MDH2-related disorder	Uncertain significance; Likely benign; Conflicting classifications of pathogenicity; Benign	rs138541865, rs149443188, rs139870141, rs376135271, rs782182384, rs2535871524, rs111879470, rs201575534, rs144919730, rs145607211	RCV003401789 RCV003950934 RCV003978519 RCV003978624 RCV003896150 RCV003899535 RCV003930666 RCV004749522 RCV003940851 RCV003953356
Melanoma	Benign	rs11538801	RCV005929826
Nonpapillary renal cell carcinoma	Benign	rs11538801, rs142812282	RCV005929811 RCV005904362
Ovarian cancer	Benign	rs11538801	RCV005929814
Ovarian serous cystadenocarcinoma	Benign	rs11538801	RCV005929822
Papillary renal cell carcinoma type 1	Uncertain significance	rs1554587656	RCV005939433
Sarcoma	Benign	rs11538801, rs142812282	RCV005929819 RCV005904366
Thymoma	Benign	rs11538801	RCV005929824
Thyroid cancer, nonmedullary, 1	Benign	rs11538801, rs142812282	RCV005929825 RCV005904367
Uterine carcinosarcoma	Benign	rs11538801	RCV005929823
Uterine corpus endometrial carcinoma	Benign	rs11538801, rs142812282	RCV005929829 RCV005904369
Uveal melanoma	Benign	rs11538801	RCV005929816

Associations from Text Mining
Disease Name	Relationship Type	References
Adenocarcinoma of Lung	Associate	38017020
Alzheimer Disease	Associate	26059363
Brain Diseases	Associate	27989324
Chronic Pain	Associate	27832094
Cystic Fibrosis	Associate	35954202
Developmental Disabilities	Associate	37977948
Diabetes Mellitus	Associate	36187097
Drug Resistant Epilepsy	Associate	27989324
Epilepsy	Associate	36079864, 37977948
Exocrine Pancreatic Insufficiency	Associate	35954202
Glomerulosclerosis Focal Segmental	Associate	36159820
Metabolic Diseases	Associate	36159820
Microcephaly	Associate	37977948
Mitochondrial Diseases	Associate	11959456
Muscle Hypotonia	Associate	27989324
Muscular Dystrophies	Associate	24920607
Neoplasms	Associate	27989324, 34494499, 36760809
Neoplasms	Stimulate	34222480
Neuroendocrine Tumors	Associate	36301191
Neurologic Manifestations	Associate	36079864, 37977948
Parkinson Disease	Associate	36593912
Pheochromocytoma	Associate	27989324, 30008476
Polycystic Ovary Syndrome	Associate	34480296
Prostatic Neoplasms	Associate	23389923
Psychomotor Disorders	Associate	27989324
Uterine Neoplasms	Associate	25639359